Immune system modifiers / Stimulants / Antibodies
3. ANTIBODIES and FUSION PROTEINS
As molecular targets are identified that distinguish cancer cells from normal cells, monoclonal antibodies have been developed that can selectively recruit the immune system to destroy the cancer cells. Currently, antibodies have been designed that target CDs (CD20 in NHL and CD52 in B-CLL), and cell surface proteins (HER2, VEGF, EGFR) that are overexpressed in specific cancers. |
![]() |
- remember the points made in the therapeutic proteins lecture!
- can test to see whether a tumour is expressing the protein target before administering drug
- currently, typically prescribed when other chemotherapy has failed, or when patient factors (esp. age) prevent the use of cytotoxic drugs
- as with antibodies used for other purposes, the goal is to get the immune system to recognize, and kill, the cell that is expressing the protein that the antibody is directed against
- i.e., the goal of an anti-CD20 antibody is to kill cells expressing CD20
- obviously, the goal here is to use the immune system to suppress itself!
TARGET |
DRUG |
USE |
CD20 |
RITUXIMAB IBRITUMOMAB (90Y) TOSITUMOMAB (131I) |
|
CD52 |
ALEMTUZUMAB |
B-cell chronic lymphocytic leukemia (B-CLL) |
DENILEUKIN DIFTITUX
- fusion protein that has diphtheria toxin coupled to IL-2
- diphtheria toxin catalyzes the ADP-ribosylation of elongation factor-2 à inhibits protein translation by inactivating EF2
- goal is to kill cells expressing IL-2 receptors (activated T-lymphocytes, B lymphocytes and macrophages)
- approved for use in cutaneous T-cell lymphoma